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Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hyperlipidemia accelerates the progression of human renal disease, and its control is becoming an important component of therapy for patients with renal failure. The biologic basis for these observations remains poorly understood. This review summarizes recent data from animal models which show how lipoproteins interact with cells directly to cause renal injury. Data are presented from recent studies on the obese Zucker rat, a metabolic model of hyperlipidemia, obesity, and glomerular sclerosis, showing that triglyceride-containing lipoproteins may mediate glomerular injury. The biochemical basis for therapy is also discussed, including actions of lipid-lowering agents apart from their effect on serum lipids, and the use of polyunsaturated fatty acids as dietary therapy. Animal models are a crucial tool for the further elucidation of mechanisms of lipoprotein-mediated glomerular injury.
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PMID:Hyperlipidemia and renal disease: the use of animal models in understanding pathophysiology and approaches to treatment. 1037 11

Membranous nephropathy (MN) is a very common cause of nephrotic syndrome in adults, and lipid abnormalities are, therefore, frequently found in these subjects. Although efficient lipid-lowering therapy is available, almost nothing is known about the contribution of hyperlipidemia in the pathogenesis of progressive renal failure in MN. Studies in an experimental animal model of human MN, Heymann nephritis, have shown that lipids play an essential role in the pathogenesis of proteinuria. Local production of reactive oxygen species after subepithelial immune complex deposition leads to the formation of lipid peroxidation (LPO) adducts, which ultimately alter the composition of the glomerular basement membrane. As the magnitude of urinary protein excretion is associated with the long-term prognosis, a normalization of glomerular permselective properties has been used as a surrogate parameter for the beneficial effects of treatment. Probucol, a drug with LPO inhibitor potential, is able to reduce urinary protein excretion in rats with passive Heymann nephritis. In humans with MN, preliminary data also support this observation. It remains to be determined, however, if this intervention, which does not interfere with immune complex formation, will reduce the number of the patients reaching end-stage renal failure because of MN. In conclusion, lipids may contribute to glomerular injury in MN, as LPO might be an especially important factor, opening the possibility for new therapeutic interventions, thereby avoiding the side-effects of the currently used treatment regimen.
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PMID:Lipid-lowering therapy in membranous nephropathy. 1041 51

Simvastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, is widely used to treat hyperlipidaemia. Although myalgias are recognized adverse effects, clinically significant elevations in serum creatine phosphokinase (CPK) levels are uncommon. We describe a case of rhabdomyolysis and acute renal failure associated with concomitant use of simvastatin and warfarin. Rhabdomyolysis and renal failure occurred 7 days after warfarin (5 mg day-1) was added to a chronic stable dose of simvastatin (20 mg day-1) and resolved abruptly after discontinuation of simvastatin. We recommend careful monitoring when warfarin is given to patients receiving simvastatin.
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PMID:Rhabdomyolysis and acute renal failure due to combination therapy with simvastatin and warfarin. 1062 Jan 5

Cerivastatin, commercialized under the trade names of Lipobay by Bayer and Cholstat by Fournier Pharma, is a new synthetic statin. Because of its high affinity for HMG-CoA reductase enzyme that it specifically and selectively inhibited in the hepatocytes, cerivastatin exerts its cholesterol-lowering effect at very low doses, between 0.1 and 0.3 mg/day. Cerivastatin is indicated, after diet failure, in the treatment of primary forms of isolated hypercholesterolaemia or combined hyperlipidaemia. It is presented by the two pharmaceutical companies as 0.1, 0.2 and 0.3 mg filmed tablets. Usual dose is 0.3 mg, once daily, to be reduced in presence of renal failure. Cerivastatin is metabolised within the liver by two different families of cytochrome P450, which limits the risk of drug interferences. Besides this potential advantage as compared with some other statins, its pharmacodynamic activity and safety profile seem to be similar to those of other agents of the same pharmacological family.
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PMID:[Pharmacy clinics. Medication of the month. Cerivastatin (Lipobay, Cholstat)]. 1076 83

Virtually all renal diseases progress to terminal renal failure relatively independently of the initial disease. Arresting the rate of the deterioration of kidney failure has a great impact on reducing the number of patients reaching the stage of expensive renal replacement therapy. Understanding the mechanisms of the progression of kidney disease has greatly been improved during recent years. The nature of the progressive renal damage with various etiologies includes various well-known factors where hemodynamics, renin-angiotensin system (RAS) and progressive proteinuria play the central roles. Proteinuria has to be shown as an independent risk factor for renal disease progression. Also, disturbances in lipid metabolism as well as the later structural lesions contribute to the progression. Various modalities have been used for the prevention of progressive renal disease, e.g. low-protein diet, antihypertensive therapy, antifibrotic therapy. Many recent experimental and clinical studies have shown that besides the systemic blood pressure lowering effect, RAS blocking agents provide renal protective effects via direct, hemodynamic, and indirect, non-hemodynamic, pathways: (1) lowering intraglomerular capillary hydraulic pressure, and increasing the glomerular ultrafiltration coefficient; (2) lowering proteinuria; (3) lowering hyperlipidemia; (4) diminishing kidney growth; (5) diminishing infiltration of macrophages; (6) downregulation of proinflammatory cytokines. Therefore, RAS blocking agents are widely prescribed not only for antihypertensive but also for renoprotective purposes in diabetic and non-diabetic nephropathies.
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PMID:Characteristics of progressive renal disease. 1084 6

The human aging process is associated with vascular endothelial dysfunction. However, humoral factors which might protect against endothelial dysfunction during aging have not yet been identified. We recently identified the klotho gene as a possible regulator of human aging. In the present study using the klotho-deficient heterozygous mouse, we examined whether the Klotho protein is a humoral factor protecting against endothelial dysfunction. We further cloned rat klotho cDNA and investigated whether klotho mRNA expression in rat kidney is altered under pathological conditions such as hypertension, hyperlipidemia, renal failure, and inflammatory stress. The Klotho protein itself, or its metabolites, promotes endothelial NO production in aorta as well as arterioles, and klotho mRNA in kidney is downregulated under sustained circulatory stress.
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PMID:Endothelial dysfunction in the klotho mouse and downregulation of klotho gene expression in various animal models of vascular and metabolic diseases. 1089 40

Left ventricular hypertrophy LVH is supposed to be a useful marker of cardiovascular complications during the course of hypertension. Occurrence of other risk factors of atherosclerosis in these hypertensive patients such as hyperlipidemia and smoking deteriorate the prognosis too. The authors compared clinical findings in hypertensive patients with and without left ventricular hypertrophy defined by echocardiography. Hospital records of 185 hypertensive patients treated at our medical department during years 1996-1999 were analysed. Left ventricular hypertrophy was defined by echocardiography (Penn convention) as left ventricular mass index > 134 g/m2 in men and > 110 g/m2 in women. Presence of LVH was found in 109 patients (mean age 66.7 years), absence of LVH in 76 patients (mean age 64.7 years). Both groups of hypertensive patients were matched by demographic parameters by the presence of hyperlipidemia and by smoking habits. Hypertensive patients with diabetes mellitus and obesity were excluded. They were statistically significant in the incidence of heart failure, myocardial infarction, renal failure and mitral regurgitation, and non-significant in the incidence of left ventricular diastolic dysfunction. There were more cardiovascular complications in LVH-positive patients than in those with LVH-negative findings. The incidence of stroke was slightly higher in LVH-negative patients. Left ventricular hypertrophy in patients with hypertension brings usually a complicated course of the disease. The authors recommend to examine the patients with arterial hypertension for the presence of left ventricular hypertrophy as it complicates the course of the disease significantly. (Tab. 3, Fig. 2, Ref. 26.)
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PMID:[Left ventricular hypertrophy in hypertension]. 1115 71

Otsuka Long-Evans Tokushima Fatty (OLETF) rats were established as a new model of non-insulin-dependent diabetes mellitus. An oral adsorbent, AST-120, is effective in removing such uremic toxins as indoxyl sulfate and delays the progression of chronic renal failure (CRF). This study was designed to determine the effects of AST-120 on the progression of CRF in uninephrectomized OLETF (1/2NxOLETF) rats and the localization of indoxyl sulfate in their kidneys. Four weeks after unilateral nephrectomy, 14 OLETF rats were divided into two groups; AST-120-administered and control 1/2NxOLETF rats. Long-Evans Tokushima Otsuka rats, which are genetically similar to the OLETF rats but not diabetic, were also included. After the administration of AST-120 for 36 weeks, we examined the effects of AST-120 on renal functional and pathological changes in the three groups. The control 1/2NxOLETF rats showed marked hyperglycemia, hyperlipidemia, renal failure, glomerular sclerosis, and tubulointerstitial injury. The administration of AST-120 to the 1/2NxOLETF rats retarded the progression of renal dysfunction and fibrosis, as well as hyperlipidemia, and reduced serum and urinary levels of indoxyl sulfate. Immunohistochemistry showed that AST-120 markedly reduced the overload of indoxyl sulfate in tubular epithelial cells, especially dilated tubules, of the 1/2NxOLETF rats. In conclusion, AST-120 delayed the progression of renal failure and fibrosis in 1/2NxOLETF rats and decreased the overload of indoxyl sulfate on renal tubular cells.
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PMID:An oral adsorbent ameliorates renal overload of indoxyl sulfate and progression of renal failure in diabetic rats. 1115 53

We evaluated cardiovascular risk factors, morbidity and mortality in patients with lupus nephritis (LN). We prospectively studied 70 consecutive patients with LN, and 70 age- and sex-matched controls with systemic lupus erythematosus (SLE) but no evidence of nephropathy, from 1988 to 1998. Patients were evaluated at entry for hypertension, diabetes, hyperlipidaemia, smoking, menopause and antiphospholipid syndrome. The LN patients (64 women, 6 men) had a mean age of 35 years (SE 1.7, range 11-67). During the 10 years, 15 (21%) LN patients and 18 (25%) of the controls were lost to follow-up. Compared with controls, LN patients had a higher prevalence of hyperlipidaemia (44% vs. 2%, p<0.001), hypertension (44% vs. 9%, p<0.001) and antiphospholipid antibodies (45% vs. 22%, p=0.01) at study onset. At the last visit, 37 (67%) LN patients had normal plasma creatinine, 13 (24%) had renal failure and only five (9%) end-stage renal failure. Hyperlipidaemia (78% vs. 27%, p<0.001) and hypertension (67% vs. 32%, p=0.01) at study onset were associated with development of renal failure. Nine LN patients and one control died (16% vs. 2%, p=0.02). These patients showed more antiphospholipid syndrome (56% vs. 17%, p=0.03) and hyperlipidaemia (78% vs. 37%, p=0.03) at study onset. The main causes of death in LN patients were vascular complications (cardiovascular or cerebrovascular events) in five patients (four of whom had antiphospholipid antibodies) and sepsis in three.
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PMID:Cardiovascular risk factors and the long-term outcome of lupus nephritis. 1116 Nov 32

The prevalence of lipid abnormalities is very high in patients with impaired renal function and after transplantation. Coronary heart disease (CHD) morbidity and mortality are impressive in these patients. No prevention study using lipid lowering agents is available in this population. Thus recommendations are still based on pathophysiological data or extrapolated from the results reported in prevention studies from kidney disease-free subjects. The treatment of hyperlipidemia can be recommended considering the expected reduction of events due to CHD. The lipid targets may be those recommended in other high risk patients: LDL-cholesterol < 120 mg/dl and triglycerides < 150 mg/dl. Unfortunately, the use of both statins and fibrates noteworthy is under restraint in case of renal failure and immunosuppressive therapy. Prospective clinical trials are needed to demonstrate the effect of lipid lowering on the course of chronic renal failure and graft dysfunction.
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PMID:[Atherosclerosis and arteriosclerosis of the small vessels in chronic renal insufficiency and after transplantation: lipid factors]. 1120 Jun 2


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